The Antipsychotic Olanzapine Interacts with the Gut Microbiome to Cause Weight Gain in Mouse

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Dec 16

PMID 25506936

Citations 90

Authors

Andrew P Morgan

James J Crowley

Randal J Nonneman

Corey R Quackenbush

Cheryl N Miller

Allison K Ryan

Molly A Bogue

Sur Herrera Paredes

Scott Yourstone

Ian M Carroll

Thomas H Kawula

Maureen A Bower

R Balfour Sartor

Patrick F Sullivan

Affiliations

Soon will be listed here.

Abstract

The second-generation antipsychotic olanzapine is effective in reducing psychotic symptoms but can cause extreme weight gain in human patients. We investigated the role of the gut microbiota in this adverse drug effect using a mouse model. First, we used germ-free C57BL/6J mice to demonstrate that gut bacteria are necessary and sufficient for weight gain caused by oral delivery of olanzapine. Second, we surveyed fecal microbiota before, during, and after treatment and found that olanzapine potentiated a shift towards an "obesogenic" bacterial profile. Finally, we demonstrated that olanzapine has antimicrobial activity in vitro against resident enteric bacterial strains. These results collectively provide strong evidence for a mechanism underlying olanzapine-induced weight gain in mouse and a hypothesis for clinical translation in human patients.

Citing Articles

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